ArticleBrain : a journal of neurology2020
Two distinct neuroanatomical subtypes of schizophrenia revealed using machine learning.
Article in Brain : a journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 3 of them syntheses that pooled it.
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Who cites it
143 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Brain structural abnormalities in treatment-resistant schizophrenia.Molecular psychiatry · 2026Pooled it
- Advances in Schizophrenia Subtyping: A Systematic Review of Machine Learning Applications in Neuroimaging.Advances in experimental medicine and biology · 2026Pooled it
- Estimating Multimodal Structural Brain Variability in Schizophrenia Spectrum Disorders: A Worldwide ENIGMA Study.The American journal of psychiatry · 2025Pooled it
- Linking Personalized Brain Atrophy to Schizophrenia Network and Treatment Response.Schizophrenia bulletin · 2023Trial
- Dynamical system modeling in schizophrenia: a narrative review of computational psychiatry frameworks.Dialogues in clinical neuroscience · 2026Review
- Connectomic signatures advance the understandings of transdiagnostic heterogeneity in psychosis.Communications medicine · 2026Review
- Neurophysiological subtyping of schizophrenia reveals a reproducible phenotype with temporoparietal circuit disruptions.General psychiatry · 2026Article
- Concomitant pathologies and their impact on schizophrenia: a narrative overview of current evidence.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Machine learning-derived Alzheimer's disease dimensions: neuroanatomical, cognitive, clinical, functional, and genetic risk heterogeneity signatures.medRxiv : the preprint server for health sciences · 2026Article
- Morphometric Inverse Divergence Networks Combined with HYDRA Identify Parkinson's Disease Subtypes with Distinct Transcriptomic and Serum Biomarker Profiles.International journal of molecular sciences · 2026Article
- Subtyping psychotic disorders using a data-driven approach reveals divergent cortical and cellular signatures.Molecular psychiatry · 2026Article
- Neuroanatomical subtypes of preterm adolescents.Molecular psychiatry · 2026Article
- Neuroimaging-Based Subgroups in Schizophrenia: A Critical Appraisal of Clustering Studies.Biological psychiatry global open science · 2026Review
- Serum LBP and zonulin levels with brain MRS findings and gastrointestinal symptoms in schizophrenia and health.Brain, behavior, & immunity - health · 2026Article
- Individualized cortical gradient and network topology reveal symptom-linked disruptions and neurobiological subtypes in schizophrenia.medRxiv : the preprint server for health sciences · 2026Article
- Integrated clinical and postmortem profiling in schizophrenia reveals a cognitive subtype linked to cerebrovascular disease.Translational psychiatry · 2026Article
- Identifying transdiagnostic neurobiomarkers for precision major psychiatric disordersJournal of translational internal medicine · 2026Article
- Cortical excitability mapping stratifies neurobiological subtypes of schizophrenia with genetic and molecular signatures.BMC medicine · 2026Article
- Multi-organ AI endophenotypes chart the heterogeneity of brain, eye and heart pan-disease.Nature. Mental health · 2026Article
- Deciphering the Heterogeneity of Schizophrenia: A Multimodal and Multivariate Neuroimaging Framework for Unveiling Brain-Symptom Relationships and Underlying Subtypes.Schizophrenia bulletin · 2026Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors.
Funding
Abstract
Neurobiological heterogeneity in schizophrenia is poorly understood and confounds current analyses. We investigated neuroanatomical subtypes in a multi-institutional multi-ethnic cohort, using novel semi-supervised machine learning methods designed to discover patterns associated with disease rather than normal anatomical variation. Structural MRI and clinical measures in established schizophrenia (n = 307) and healthy controls (n = 364) were analysed across three sites of PHENOM (Psychosis Heterogeneity Evaluated via Dimensional Neuroimaging) consortium. Regional volumetric measures of grey matter, white matter, and CSF were used to identify distinct and reproducible neuroanatomical subtypes of schizophrenia. Two distinct neuroanatomical subtypes were found. Subtype 1 showed widespread lower grey matter volumes, most prominent in thalamus, nucleus accumbens, medial temporal, medial prefrontal/frontal and insular cortices. Subtype 2 showed increased volume in the basal ganglia and internal capsule, and otherwise normal brain volumes. Grey matter volume correlated negatively with illness duration in Subtype 1 (r = -0.201, P = 0.016) but not in Subtype 2 (r = -0.045, P = 0.652), potentially indicating different underlying neuropathological processes. The subtypes did not differ in age (t = -1.603, df = 305, P = 0.109), sex (chi-square = 0.013, df = 1, P = 0.910), illness duration (t = -0.167, df = 277, P = 0.868), antipsychotic dose (t = -0.439, df = 210, P = 0.521), age of illness onset (t = -1.355, df = 277, P = 0.177), positive symptoms (t = 0.249, df = 289, P = 0.803), negative symptoms (t = 0.151, df = 289, P = 0.879), or antipsychotic type (chi-square = 6.670, df = 3, P = 0.083). Subtype 1 had lower educational attainment than Subtype 2 (chi-square = 6.389, df = 2, P = 0.041). In conclusion, we discovered two distinct and highly reproducible neuroanatomical subtypes. Subtype 1 displayed widespread volume reduction correlating with illness duration, and worse premorbid functioning. Subtype 2 had normal and stable anatomy, except for larger basal ganglia and internal capsule, not explained by antipsychotic dose. These subtypes challenge the notion that brain volume loss is a general feature of schizophrenia and suggest differential aetiologies. They can facilitate strategies for clinical trial enrichment and stratification, and precision diagnostics.
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